Bacterial infections are the primary cause of otitis media with effusion (OME), an inflammatory disease of the middle ear. OME is characterized by production of pro-inflammatory cytokines within the middle ear and development of inflammation and fluid accumulation. While the primary treatment for OME is antibiotics, there is no therapy that directly targets the inflammation and fluid accumulation. This Phase II proposal will provide pre-clinical assessment of a therapy to treat bacterial-induced inflammation. Targeted Gene Delivery has developed a novel peptide drug that specifically blocks the intracellular signaling and cell activation (production of pro-inflammatory cytokines) that results from the interaction of bacteria and immune cells. Preliminary in vivo studies demonstrated a significant anti-inflammatory effect in a mouse model of bacterial induced OME, with marked reduction in fluid accumulation, number of inflammatory cells, and mucosal thickening in the middle ear. In the current study, experiments will test the efficacy of this therapy in reducing inflammation in a mouse model of bacterial-induced OME and the impact of this novel therapy on improving hearing thresholds. These studies have the potential to define a new approach to treating bacterial-induced inflammation that will have application in OME and a variety of other inflammatory diseases.